Journal article
Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect Study
Antimicrobial agents and chemotherapy, Vol.64(11), e01018-20
11/01/2020
DOI: 10.1128/AAC.01018-20
PMCID: PMC7577123
PMID: 32816721
Abstract
Neurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human use, phase I multiple ascending dose and food effect studies were conducted. Thirty-six healthy adults were enrolled in an open-label study which evaluated (i) the pharmacokinetics and safety of oxfendazole following multiple ascending doses of oxfendazole oral suspension at 3, 7.5, and 15 mg/kg once daily for 5 days and (ii) the effect of food on oxfendazole pharmacokinetics and safety after a single 3-mg/kg dose administered following an overnight fast or the consumption of a fatty breakfast. Following multiple oral dose administration, the intestinal absorption of oxfendazole was rapid, with the time to maximum concentration of drug in serum (T-max) ranging from 1.92 to 2.56 h. A similar half-life of oxfendazole (9.21 to 11.8 h) was observed across all dose groups evaluated, and oxfendazole exhibited significantly less than a dose-proportional increase in exposure. Oxfendazole plasma exposures were higher in female subjects than in male subjects. Following daily administration, oxfendazole reached a steady state in plasma on study day 3, with minimal accumulation. Food delayed the oxfendazole Tmax by a median of 6.88 h and resulted in a 49.2% increase in the maximum observed drug concentration in plasma (C-max) and an 86.4% increase in the area under the concentration-time curve (AUC). Oxfendazole was well tolerated in all study groups, and there were no major safety signals identified in this study.
Details
- Title: Subtitle
- Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect Study
- Creators
- Thanh Bach - University of IowaShirley Galbiati - EmmesJessie K. Kennedy - EmmesGregory Deye - National Institute of Allergy and Infectious DiseasesEffie Y. H. Nomicos - National Institute of Allergy and Infectious DiseasesEllen E. CoddHector H. Garcia - Universidad Peruana Cayetano HerediaJohn Horton - Oxfendazole Development GroupRobert H. Gilman - Johns Hopkins UniversityArmando E. Gonzalez - Universidad Peruana Cayetano HerediaPatricia Winokur - Roy J. and Lucille A. Carver College of MedicineGuohua An - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.64(11), e01018-20
- Publisher
- Amer Soc Microbiology
- DOI
- 10.1128/AAC.01018-20
- PMID
- 32816721
- PMCID
- PMC7577123
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Number of pages
- 16
- Grant note
- 5U54TR001356 / National Center for Advancing Translational Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) HHSN272200800008C; HHSN272201300020I / Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, through the Vaccine and Treatment Evaluation Unit
- Language
- English
- Date published
- 11/01/2020
- Academic Unit
- Infectious Diseases; Pharmaceutical Sciences and Experimental Therapeutics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984359793402771
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